Incidence and Predictors of Seizures in Patients with Alzheimer's Disease

Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Epilepsia (Impact Factor: 4.57). 06/2006; 47(5):867-72. DOI: 10.1111/j.1528-1167.2006.00554.x
Source: PubMed


To determine cumulative incidence and predictors of new-onset seizures in mild Alzheimer's disease (AD) with a cohort followed prospectively. Limited information is available on the incidence of seizures, and no reports exist of seizure predictors in AD patients.
Mild AD patients were prospectively followed at 6-month intervals to estimate incidence of unprovoked seizures, compare age-specific risk of unprovoked seizures with population norms, and identify characteristics at baseline (demographics, duration and severity of AD, physical and diagnostic test findings, and comorbid medical and psychiatric conditions) influencing unprovoked seizure risk. Review of study charts and medical records supplemented coded end-point data.
The cumulative incidence of unprovoked seizures at 7 years was nearly 8%. In all age groups, risk was increased compared with a standard population, with an 87-fold increase in the youngest group (age 50-59 years) and more than a threefold increase in the oldest group (age 85+ years). In multivariate modeling, independent predictors of unprovoked seizures were younger age [relative risk (RR), 0.89 per year increase in age; 95% confidence interval (CI), 0.82-0.97], African-American ethnic background (RR, 7.35; 95% CI, 1.42-37.98), more-severe dementia (RR, 4.15; 95% CI, 1.06-16.27), and focal epileptiform findings on electroencephalogram (EEG) (RR, 73.36; 95% CI, 1.75-3075.25).
Seizure incidence is increased in people starting with mild-to-moderate AD. Younger individuals, African Americans, and those with more-severe disease or focal epileptiform findings on EEG were more likely to have unprovoked seizures.

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Available from: Jason Brandt, Jan 08, 2014
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    • "The risk of unprovoked epileptic seizures is rather high in earlyonset (often familial) Alzheimer's disease, perhaps as much as ~ 90- fold higher than in an age-matched reference population (Amatniek et al., 2006). Importantly, epileptic activity may also be more prevalent in the early stages of 'sporadic' late-onset AD than was previously thought (Vossel et al., 2013), but the underlying mechanisms are poorly understood. "
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    ABSTRACT: Epileptic activity may be more prevalent in early stage Alzheimer's disease (AD) than previously believed. Several studies report spontaneous seizures and interictal discharges in mouse models of AD undergoing age-related Aβ accumulation. The mechanism by which Aβ-induced neuronal excitability can trigger epileptiform activity remains unknown. Here, we systematically examined field excitatory postsynaptic potentials (fEPSP) in stratum radiatum and population spikes (PSs) in the adjacent stratum pyramidale of CA1 in wild-type mouse hippocampal slices. Soluble Aβ oligomers (oAβ) blocked hippocampal LTP and EPSP-spike (E-S) potentiation, and these effects were occluded by prior treatment with the glutamate uptake inhibitor TBOA. In accord, oAβ elevated glutamate levels in the hippocampal slice medium. Recording the PS revealed that oAβ increased PS frequency and reduced LTP, and this LTP deficit was occluded by pretreatment with the GABAA antagonist picrotoxin. Whole-cell recordings showed that oAβ significantly increased spontaneous EPSC frequency. Decreasing neuronal activity by increasing GABA tone or partially blocking NMDAR activity prevented oAβ impairment of hippocampal LTP. Finally, treating slices with two antiepileptic drugs rescued the LTP inhibition induced by oAβ. We conclude that soluble Aβ oligomers at the low nanomolar levels present in AD brain increase neuronal excitability by disrupting glutamatergic/GABAergic balance, thereby impairing synaptic plasticity.
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    • "Amongst early events linked to AD pathogenesis that can contribute to memory decline, we focused here on neuronal network hypersynchrony (Bakker et al., 2012; Vossel et al., 2013). Indeed, seizures are more frequent in AD patients than in age-matched individuals and seizures can precede the onset of memory deficits (Amatniek et al., 2006; Sanchez et al., 2012). Different lines of evidence also indicate the occurrence of hypersynchronous network activity such as seizures amongst mouse models of AD (Palop et al., 2007; Minkeviciene et al., 2009; Born et al., 2014; Ittner et al., 2014). "
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    ABSTRACT: The cognitive reserve hypothesis claims that the brain can overcome pathology by reinforcing preexistent processes or by developing alternative cognitive strategies. Epidemiological studies have revealed that this reserve can be built throughout life experiences as education or leisure activities. We previously showed that an early transient environmental enrichment (EE) durably improves memory performances in the Tg2576 mouse model of Alzheimer's disease (AD). Recently, we evidenced a hypersynchronous brain network activity in young adult Tg2576 mice. As aberrant oscillatory activity can contribute to memory deficits, we wondered whether the long-lasting memory improvements observed after EE were associated with a reduction of neuronal network hypersynchrony. Thus, we exposed non-transgenic (NTg) and Tg2576 mice to standard or enriched housing conditions for 10 weeks, starting at 3 months of age. Two weeks after EE period, Tg2576 mice presented similar seizure susceptibility to a GABA receptor antagonist. Immediately after and 2 weeks after this enrichment period, standard and enriched-housed Tg2576 mice did not differ with regards to the frequency of interictal spikes on their electroencephalographic (EEG) recordings. Thus, the long-lasting effect of this EE protocol on memory capacities in Tg2576 mice is not mediated by a reduction of their cerebral aberrant neuronal activity at early ages.
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    • "The prevalence of seizures in AD varies between studies, but is in the range of 10–22 % (Mendez and Lim 2003). Seizure susceptibility increases with progression of the disease (Romanelli et al. 1990), and seizures are more frequent in patients with early disease onset (Amatniek et al. 2006). Amnestic episodes in patients are associated with seizures recorded by EEG, indicating that seizures not only are a concomitant phenomenon of AD, but may actually contribute to the symptoms of dementia (Rabinowicz et al. 2000). "
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